NIDA and a number of pharmaceutical companies are devoting substantial resources to the development of new medications for the treatment of cocaine abuse. The widespread use of cocaine and the multiplicity of toxic social and individual consequences associated with its use (e.g., its role in the spread of AIDS) makes imperative the control of this severe public health problem. Currently, few procedures, other than costly and time consuming controlled double-blind clinical trials, exist for evaluating new medications in humans. In addition, there are minimal data on the relationship between cocaine-taking and maintenance on possible treatment agents for cocaine abusers. Therefore, laboratory procedures in which a range of cocaine's effects can be measured, and the interaction of cocaine with potential treatment medications monitored, are clearly needed. The currently proposed research uses a laboratory intravenous cocaine self- administration procedure in which non-drug options are also available and contingencies support some choice of the non-drug option. This research will evaluate cocaine-taking behavior as well as its subjective effects, "craving," and its physiological effects before and during maintenance on carbamazepine, sertraline and ritanserin, three currently proposed pharmacotherapies. As new agents are proposed, they too will be evaluated. Subjects will be tested under conditions in which they are maintained, as well as when they are not maintained, on a potential treatment medication. Importantly, these data will allow assessment of medication efficacy based on the behavioral mechanism of action of each of the pharmacological agents proposed for the treatment of cocaine abuse (i.e., does it interact with cocaine's reinforcing effects. Its subjective effects or cocaine craving). Since cocaine abstinence is the most desired treatment outcome, laboratory procedures in which the behavior of cocaine self-administration is specifically measured under conditions comparable to those outside of the laboratory will be used to assess potential pharmacotherapeutic agents. As with cocaine use outside of the laboratory, repeated doses will be available, and effects on "binge" behavior measured. Continued development of this model will enable more rapid assessment of promising agents, thereby guiding decisions regarding which of the potentially useful therapeutic agents should be evaluated with costlier and more arduous double-blind clinical trials. In addition, this laboratory approach will provide considerably, more information about the behavioral mechanisms of action of the compounds being tested than might be gained with clinical trials alone. The proposed research investigates the multiplicity of ways that a drug treatment could enhance cocaine abstinence. The data thus collected will suggest more efficacious approaches to treating cocaine abusers, and will contribute to the continuing development of a laboratory model for evaluating potential new medications for the treatment of cocaine abuse.